Molecular dynamics analysis of phytochemicals from Ageratina adenophora against COVID-19 main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE2)

Neupane, Netra Prasad; Karn, Abhishek Kumar; Mukeri, Imdad Husen; Pathak, Prateek; Kumar, Praveen; Singh, Samayaditya; Qureshi, Insaf Ahmed; Jha, Tarun; Verma, Amita

doi:10.1016/j.bcab.2021.101924

Cited by 17 publications

(10 citation statements)

References 28 publications

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“…These results were further confirmed by Jang et al [57]. 3-O-Caffeoylquinic acid and methyl 3,5-di-O-caffeoyl quinate showed better binding to SARS CoV-2 Mpro as compared to remdesivir [58]. Ravi [59] reported that the hot aqueous fruit pulp extract of Cassia fistula rich in Procyanidin B2 can be used to allievate COVID patients based on a molecular dynamics study.…”

Section: Resultssupporting

confidence: 53%

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Mostafa¹,

Ismail²,

El-Araby³

et al. 2022

Phyton

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Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals. The primary treatment is either supportive or symptomatic. Natural products have an important role in the development of various drugs. Thus, screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses. In the current study, an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents, (e.g., procyanidin B2, theaflavin, quercetin, ellagic acid, caffeoylquinic acid derivatives, berginin, eudesm-1β, 6α, 11-triol and arbutin), on the crystal structure of SARS-CoV-2 main protease (PDB ID: 6w63) using AutoDock-Vina software. Many of the docked compounds revealed good binding affinity, with procyanidin B2 (-8.6 Kcal/mol) and theaflavin (-8.5 Kcal/mol) showing a better or similar binding score as the ligand (-8.5 Kcal/mol). Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin. Procyanidin B2, theaflavin, and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways. Additionally, these phytoconstituents showed good ADME properties and acceptable lipophilicity, as evaluated using WLOGP. Amongst the tested compounds, procyanidin B2 showed the highest lipophilic value. It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns.

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Section: Resultssupporting

confidence: 53%

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Mostafa¹,

Ismail²,

El-Araby³

et al. 2022

Phyton

View full text Add to dashboard Cite

show abstract

“…The host nuclear import system can be bound and sequestered by pathogens such as SARS-CoV-2 allowing transportation of viral proteins to the host nucleus leading to increased viral replication [ [12] , [13] , [14] , [15] ]. Additionally, we also consider the multi-functional helicase (nsp13) of SARS-CoV-2 responsible for viral replication (PDB: 6ZSL ) [ [16] , [17] , [18] ], and the main protease (Mpro) of SARS-CoV-2 (PDB: 6LU7 ) as it is a key enzyme of coronaviruses and has a fundamental role in mediating viral replication and transcription, making it an attractive target for drugs [ 11 , [19] , [20] , [21] , [22] ]. All structures were obtained in PDB format from the RCSB protein database ( https://www.rcsb.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

González

Hurtado-León

Lossada

et al. 2021

Biophysical Chemistry

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The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro . However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior.

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“…The host nuclear import system can be bound and sequestered by pathogens such as SARS-CoV-2 allowing transportation of viral proteins to the host nucleus leading to increased viral replication [25] , [26] , [27] , [28] , [29] . Additionally, we also consider the multi-functional helicase (nsp13) of SARS-CoV-2 responsible for viral replication (PDB: 6ZSL) [30] , [31] , [32] , and the main protease (Mpro) of SARS-CoV-2 (PDB: 6LU7) as it is a key enzyme of coronaviruses and has a fundamental role in mediating viral replication and transcription, making it an attractive target for drugs [33] , [34] , [35] , [36] , [37] . All structures were obtained in PDB format from the RCSB Protein Data Bank ( https://www.rcsb.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models

González

Hurtado-León

Lossada

et al. 2021

Journal of Molecular Liquids

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The COVID-19 pandemic has accelerated the study of the potential of multi-target drugs (MTDs). The mixture of homologues called ivermectin (avermectin-B1a + avermectin-B1b) has been shown to be a MTD with potential antiviral activity against SARS-CoV-2 in vitro . However, there are few reports on the effect of each homologue on the flexibility and stiffness of proteins associated with COVID-19, described as ivermectin targets. We observed that each homologue was stably bound to identified proteinsthe proteins studied and were able to induce detectable changes with Elastic Network Models (ENMs). The perturbations induced by each homologue were characteristic of each compound and, in turn, were represented by a disruption of native intramolecular networks (interactions between residues). The homologues were able to slightly modify the conformation and stability of the connection points between the Cα atoms of the residues that make up the structural network of proteins (nodes), compared to free proteins. Each homologue was able to modified differently the distribution of quasi-rigid regions of the proteins, which could theoretically alter their biological activities. These results could provide a biophysical-computational view of the potential MTD mechanism that has been reported for ivermectin.

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Molecular dynamics analysis of phytochemicals from Ageratina adenophora against COVID-19 main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE2)

Cited by 17 publications

References 28 publications

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models

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